A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 22, 2021

Abstract There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine SARS-CoV-2. The based on display of coronavirus spike glycoprotein receptor-binding domain (RBD) synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses RBD-SpyVLP in prime-boost regimen induce strong neutralising antibody response mice pigs that superior convalescent human sera. We evaluate quality ACE2 blocking neutralisation cell infection by pseudovirus or wild-type Using competition assays with monoclonal panel, show induces polyclonal recognises key epitopes RBD, reducing likelihood selecting neutralisation-escape mutants. Moreover, thermostable can be lyophilised without losing immunogenicity, facilitate global distribution reduce cold-chain dependence. data suggests provides potential address clinical logistic challenges COVID-19

Language: Английский

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Engineered ACE2 receptor traps potently neutralize SARS-CoV-2

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(45), P. 28046 - 28055

Published: Oct. 22, 2020

Significance During the ongoing COVID-19 pandemic, protein engineering offers a rapid and powerful approach for building therapeutics to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We use computational design, affinity maturation, fusion dimerization domains engineer “receptor traps” based on wild-type angiotensin-converting enzyme II (ACE2), target viral spike-mediated SARS-CoV-2 entry into cells. The optimized ACE2 receptor traps neutralize authentic infections as effectively high-affinity antibodies isolated from convalescent patients also bind spike proteins other coronaviruses known cause diseases. have large binding interfaces block entire interface, limiting potential impact of escape mutations.

Language: Английский

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Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Jan. 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity reliability, monoclonal antibodies (mAbs) have emerged as powerful tools treat detect numerous diseases. Hence, many researchers begun urgently develop Ab-based kits for detection severe acute respiratory syndrome 2 (SARS-CoV-2) Ab drugs use COVID-19 therapeutic agents. detailed structure SARS-CoV-2 spike protein known, since this key infection, its receptor-binding domain (RBD) has become a major target development. Because RNA virus with mutation rate, especially under selective pressure aggressively deployed prophylactic vaccines neutralizing Abs, cocktails expected be important strategy effective treatment. Moreover, infection may stimulate overactive immune response, resulting in cytokine storm drives progression. Abs combat storms also been intense development treatments COVID-19. In addition drugs, are currently being utilized tests, including antigen immunoglobulin tests. Such tests crucial surveillance can used prevent spread Herein, we highlight some points regarding mAb-based pandemic.

Language: Английский

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Recognition of the SARS-CoV-2 receptor binding domain by neutralizing antibodies

Biochemical and Biophysical Research Communications, Journal Year: 2020, Volume and Issue: 538, P. 192 - 203

Published: Oct. 10, 2020

Immediately from the outset of COVID-19 pandemic, researchers diverse biomedical and biological disciplines have united to study novel pandemic virus, SARS-CoV-2. The antibody response SARS-CoV-2 has been a major focus research due its clinical relevance importance in vaccine therapeutic development. Isolation characterization antibodies accumulating at an unprecedented pace. Most neutralizing date target spike (S) protein receptor binding domain (RBD), which engages host ACE2 for viral entry. Here we review sites molecular features monoclonal that RBD, including few also cross-neutralize SARS-CoV.

Language: Английский

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NANOBODIES®: A Review of Diagnostic and Therapeutic Applications

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5994 - 5994

Published: March 22, 2023

NANOBODY® (a registered trademark of Ablynx N.V) molecules (Nbs), also referred to as single domain-based VHHs, are antibody fragments derived from heavy-chain only IgG antibodies found in the

Language: Английский

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Antibodies and Vaccines Target RBD of SARS-CoV-2

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: April 22, 2021

The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which gives rise to the coronavirus disease 2019 (COVID-19), has caused a serious threat global public health. On March 11, 2020, WHO had officially announced COVID-19 as pandemic. Therefore, it is vital find effective and safe neutralizing antibodies vaccines for COVID-19. critical domain (CND) that contained in receptor-binding (RBD) of spike protein (S protein) could lead highly potent antibody response well cross-protection other strains SARS. By using RBD an antigen, many are isolated essential therapeutics Furthermore, subunit vaccine, based on RBD, expected be safer than others, thus S more important target vaccine development. In this review, we focus targeting under current

Language: Английский

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Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(19)

Published: April 23, 2021

Significance Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics the prevention treatment of COVID-19. We identified high-affinity nanobodies SARS-CoV-2 receptor-binding domain found that nanobody cocktails consisting two noncompeting were able to block ACE2 engagement with RBD variants present in human populations potently neutralize both wild-type N501Y D614G variant at low concentrations. Prophylactic administration reduced viral loads mice infected virus, showing useful prophylactic agents SARS-CoV-2.

Language: Английский

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Current Prevention of COVID-19: Natural Products and Herbal Medicine

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 16, 2020

Starting from December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and unprecedented health crisis across the globe. While development of cure is at full speed, less attention fewer effort have been spent on prevention this rapidly spreading respiratory infectious disease. Although so far, several vaccine candidates advanced into clinical trials, limited data released regarding efficacy safety in human, not mention long-term effectiveness those vaccines remain as open question yet. Natural products herbal medicines historically used for acute infection generally show acceptable toxicity. The favorable stability oral formulation ease scaling up manufacture make it ideal candidate prophylactic. Hereby, we summarized most recent advance SARS-CoV-2 including well experimental prophylactics. Mainly, reviewed natural showing inhibitory effect human coronavirus, discussed lately COVID-19, especially focused already approved by regulatory agency with identifiable patent number. We demonstrated that to fill response gap between appropriate treatment commercially available vaccine, repurposing prophylactic will be a vigorous approach stop or least slow down transmission. In interest public health, lend officials better control current pandemic.

Language: Английский

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A SARS‐CoV‐2 Spike Binding DNA Aptamer that Inhibits Pseudovirus Infection by an RBD‐Independent Mechanism**

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(18), P. 10279 - 10285

Published: March 8, 2021

The receptor binding domain (RBD) of the spike glycoprotein coronavirus SARS-CoV-2 (CoV2-S) binds to human angiotensin-converting enzyme 2 (ACE2) representing initial contact point for leveraging infection cascade. We used an automated selection process and identified aptamer that specifically interacts with CoV2-S. does not bind RBD CoV2-S block interaction ACE2. Nevertheless, studies revealed potent specific inhibition pseudoviral by aptamer. present study opens up new vistas in developing SARS-CoV2 inhibitors, independent blocking ACE2 virus, harnesses aptamers as potential drug candidates tools disentangle hitherto inaccessible modalities, which is particular interest light increasing number escape mutants are currently being reported.

Language: Английский

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A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 22, 2021

SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four (C5, H3, C1, F2) engineered homotrimers pmolar affinity the receptor binding (RBD) of spike protein. Crystal structures show C5 H3 overlap ACE2 epitope, whilst C1 F2 bind different epitope. Cryo Electron Microscopy shows results in all down arrangement Spike neutralize Victoria strain, highly transmissible Alpha (B.1.1.7 first identified Kent, UK) strain also neutralizes Beta (B.1.35, South Africa). Administration C5-trimer via route showed potent therapeutic efficacy Syrian hamster model separately, prophylaxis. The molecule was similarly by intraperitoneal injection.

Language: Английский

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